Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) induces IL-6 production through TAK-1/JNK/AP-1 and TAK-1/NF-κB signaling pathways

Porcine reproductive and respiratory syndrome virus (PRRSV) mainly infects monocyte/macrophage lineage and regulates the production of cytokines to influence host immune responses. Interleukin-6 (IL-6) is originally identified as a B-cell stimulatory factor and has important functions in regulating immune response, hemopoiesis, and inflammation. In this study, we verified that highly pathogenic PRRSV (HP-PRRSV) infection up-regulated IL-6 production in vivo and in vitro. Subsequently, we demonstrated that HP-PRRSV infection activated JNK and NF-kappa B signaling pathways to enhance IL-6 expression. We further showed that TAK-1 was important in the activation of JNK and NF-kappa B pathways following HP-PRRSV infection. Moreover, AP-1 and NF-kappa B binding motifs were found in the cloned porcine IL-6 (pIL-6) promoter, and deletion of these motifs abrogated the activation of pIL-6 promoter by HP-PRRSV, suggesting that IL-6 expression is dependent on AP-1 and NF-kappa B activation. These findings imply that IL-6 induced by HP-PRRSV infection is dependent on the activation of TAK-1/JNK/AP-1 and TAK-1/NF-kappa B signaling pathways.

Automated summary

Highly pathogenic PRRSV infection enhances IL-6 production and expression through activation of JNK and NF-κB signaling pathways. TAK-1 plays a crucial role in the activation of JNK and NF-κB pathways following HP-PRRSV infection, indicating the dependence of IL-6 expression on AP-1 and NF-κB activation.